吲哚啉类α_1-肾上腺素受体拮抗剂的合成及生物活性

Synthesis and biological activity of indoline compounds as α_1-AR antagonist

目的:寻找新的α1-肾上腺素受体(α1-AR)拮抗剂。方法:以西洛多辛为先导化合物,保留其药效基团吲哚啉母核,依据拼合原理,引入取代苯氧基烷基哌嗪基团,设计合成了12个5-[2-[4-(取代苯氧基烷基)-1-哌嗪基]丙基]吲哚啉类化合物。结果:目标化合物结构经元素分析、红外光谱、质谱和核磁共振氢谱确证,初步药理实验结果表明,6个目标化合物的拮抗参数pA2值大于7.50,具有较好的α1-AR拮抗活性。结论:5-[2-[4-(取代苯氧基烷基)-1-哌嗪基]丙基]吲哚啉类化合物是一类新型的具有潜在价值的α1-AR拮抗剂。

Aim： To search for novel α1-adrenoceptor（α1-AR） antagonists. Methods： On the basis of hybridization principle with silodosin as the lead compound, twelve 5-[ 2-[ 4-[ （ substituted phenoxy） alkyl] piperazin-l-yl] propyl] indoline compounds were designed and synthesized by maintaining indoline while incorporating the 1-[ （ substituted phenoxy） alkyl] piperazine group. Results： The structures of synthesized target compounds were confirmed by the elemental analysis, IR, ESI-MS and 1H NMR. Preliminary pharmacological test showed that pA2 values of six target compounds were greater than 7.50, which suggested that the compounds possessed considerable α1 -AR antagonic activity. Conclusion： 5-[ 2-[ 4-[ （ substituted phenoxy） alkyl] piperazin-I -yl] propyl] indoline compounds is potentially a new candidate for α1-AR antagonist.